1. Field of the Invention
The U.S. poultry industry has experienced important economic losses as a result of avian coccidiosis, the major parasitic disease of poultry. This invention relates to a mushroom lectin extracted from Fomitella fraxinea, FFrL, and pharmaceutical compositions comprising FFrL which have immunopotentiating effects on poultry cell-mediated immunity and can be used in a strategy to control coccidiosis in the poultry supply.
2. Description of the Relevant Art
Mushrooms and mushroom lectins have recently gained significant attention in medical research due to their immunoenhancing effects and their demonstrated potential in promoting health (Borchers et al. 2004. Exp. Biol. Med. 229:393-406). Lectins are carbohydrate-binding proteins or glycoproteins of non-immune origins, which have the ability to induce cell agglutination (Goldstein et al. 1980. Nature 285: 66). They have been found in diverse living organisms including animals, plants and microorganisms (Cammue et al. 1985. Eur. J. Biochem. 148:315-322; Suzuki, Y. 1985. Bull. Jap. Soc. Sci. Fish. 51:2083; Avichezer and Gilboa-Garber. 1991. Toxicon 29:1305-1313). Lately, there has been a growing interest in lectins specifically, largely due to the discovery that some lectins exert various important biological activities including immunomodulatory activities (Ribéreau-Gayon et al. 1996. Cancer Lett. 109: 33-38; Wang et al. 1996. Immunopharmacology 31:205-211; She et al. 1998. Biochem. Biophys. Res. Commun. 247:106-111; Lima et al. 1999. Immunopharmacology 41:147-155; Suvachittanont and Jaranchavanapet. 2000. Planta Medica 66:699-704; Ho et al. 2004. Biochem. Biophys. Acta 1671:9-17), anti-proliferative/anti-tumor activities (Wang et al., supra; Abdullaev and de Mejia. 1997. Toxins 5:157-163; Yoon et al. 1999. Cancer Lett. 136:33-40; Karasaki et al. 2001. Food Res. Int. 34:7-13; Zhao et al. 2003. Biochem. J. 374:321-327; Ngai and Ng. 2004. Biochem. Biophys. Res. Commun. 314:988-993), antifungal activities (Gozia et al. 1993. FEBS Lett. 370:245-249; Ye et al. 2001. J. Protein Chem. 20:367-375) and anti-viral activities (Marchetti et al. 1995. Res. Virol. 146:211-215; Ye et al., supra). Although many mushroom lectins have been isolated and characterized (Guillot and Konska. 1997. Biochem. Syst. Ecol. 25:203-230), only some of them have been shown to possess immunomodulatory and anti-tumor activity (Wang et al. 1996, supra; Wang et al. 2002. Life Sci. 70:877-885; She et al., supra). More recently, some mushroom extracts were shown to have immunoenhancing potential in chickens (Guo et al. 2004. Poult. Sci. 83:1124-1132; Guo et al., 2005. Avian Dis. 49:70-73) particularly during coccidiosis.
Avian coccidiosis is the major parasitic disease of poultry with substantial economic burden to the industry. In-feed medication for prevention and treatment of coccidiosis contributes to a major portion of the economic costs. Additional economic losses associated with coccidiosis are mortality, malabsorption, inefficient feed utilization and impaired growth rate in broilers, and a temporary reduction of egg production in layers. Coccidiosis is caused by several apicomplexan parasites of the genus Eimeria that infect the intestinal tract and are transmitted between birds via ingestion of infective oocysts during feeding. While natural infection and live oocyst vaccination with Eimeria spp. induces immunity, disease control remains largely dependent on routine use of anti-coccidial drugs (Lillehoj et al., 2004. Poult. Sci. 83:611-623; Dalloul and Lillehoj. 2005. Avian Dis. 49:1-8). The poultry industry in the United States as well as worldwide has relied heavily upon prophylactic chemotherapy resulting in the development of resistant strains of Eimeria to all introduced anticoccidial drugs (Chapman, H. D. 1997. Avian Pathol. 26:221-244). Therefore, the lack of efficient vaccines, the increasing incidence of drug resistant strains, escalating public anxiety over chemical residues in meat and eggs as well as regulatory bans of growth promoting drugs in poultry production, mandate the development of alternative control methods.
Therefore, recent research has focused on the development of alternative disease control strategies including the introduction of alternative prevention/treatment measures such as non-chemical feed supplements (Dalloul et al. 2003a. Poult. Sci. 82: 62-66; Dalloul et al. 2003b. Avian Dis. 47:1313-1320), novel and effective vaccines, including recombinant vaccines (Ding et al. 2004. Infect. Immun. 72:6939-6944; Ding et al. 2005. Vaccine 23:3733-3740; Min et al. 2003. Vaccine 20:267-274; Lillehoj et al., 2004, supra; Lillehoj et al., 2005. Avian Dis. 49:112-117 and live vaccines (Weber et al. 2004. Poult. Sci. 83:392-399); and other immunization strategies such as the use of CpG oligodeoxynucleotides (Dalloul et al. 2005. Vaccine 23:3108-3113) and mushroom and herb extracts (Guo et al. 2004 and 2005, supra).
There continues to be a need for alternative strategies to control avian coccidiosis caused by Eimeria. We have investigated the effects of a mushroom-derived lectin in inducing immunoprotection against an Eimeria challenge.